Morphogenesis plays a major role in developmental and malignant systems. There are, however, no satisfactory explanations at either the cellular or molecular level for these cell movements. The goal of the proposed research is to determine first the importance of intercellular adhesive specificity in these movements and, second, to investigate the molecular bases for these specificities. The relationship of adhesive specificity to morphogenetic movements will be investigated using the collecting aggregate assay. This assay measures and compares the numbers of isotopically labeled cells collected by unlabeled aggregates of different types when these aggregates are circulated in the labeled cell suspension. The systems we will explore in detail are those using normal and malignant cultured fibroblasts and the highly ordered retinotectal connections in the developing chick embryo. The molecular anatomy of the specificity-conferring compounds will be determined using specific enzymes. Since the activities of the enzymes will be known, the structures being affected will similarly be known. Preliminary experiments of these kinds have been successful in the fibroblast and retinotectal systems. Further work on the nature of the molecular mechanism behind intercellular recognition will consist of two specific tests of the roles played by cell surface glycosyltransferases and their respective oligosaccharide substrates. These moieties have been found on retina cells of the chick embryo, human platelets, mouse fibroblasts, and rat intestinal epithelia. In all of these cases, they have been associated with recognition and communication between cells. We plan to test their roles using two morphogenetic mutations, reeler and Brachyury, in mice. These mutations cause defects which occur at specific times and places in mouse development. We will look for corresponding transferase aberrencies in these systems. Preliminary data with the reeler are quite promising.